The overall objective of these studies is to understand the consequences of specific replacements of amino acid residues in the reactive site of protein proteinase inhibitors and to explain why frequent changes of such residues occur during evolution. Most of the work will focus on ovomucoids of many birds and hopefully of other vertebrates. The principal methods of attack are amino acid sequencing, specific residue replacement, physicochemical studies on enzyme-inhibitor association, separation and characterization of ovomucoid domains. A collateral benefit of these studies may be that characterized ovomucoid domains may prove useful in inhibitor replacement therapy, for example as means of protection against pulmonary emphysema and some blood clotting disorders.